Osteoarthritis is the most common musculoskeletal disease in the United States and throughout the world. While predisposing conditions have been identified, the actual cause of osteoarthritis remains unknown and therapy at present is limited to relief of symptoms. Traditional treatments, most often nonsteroidal anti-inflammatory drugs and nonnarcotic analgesics such as acetaminophen, produce variable efficacy and may be complicated by significant toxicity. The use of alternative and complementary therapies in the treatment of osteoarthritis is common and particular interest has focused on glucosamine and chondroitin preparations. Numerous anecdotal and preliminary reports with these agents have ted to present NIAMS/NCCAM sponsored Glucosamine Arthritis Intervention Trial (GAIT). The specific aims of this multi-center trial are to determine to determine the efficacy of glucosamine, chondroitin, and the combination in relieving the symptoms of knee osteoarthritis and to investigate the possibility of a chondroprotective effect. A number of biologic actions have been attributed to glucosamine and chondroitin but no convincing mechanism of action is apparent. The specific aim of this study is to determine the single-dose and multiple-dose pharmacokinetics of these agents when used individually as well as in combination. The study medications and dosing regimens to be investigated are those being utilized in GAIT. A better understanding of the pharmacokinetics of these agents may provide a more rational basis for future clinical investigations as well as suggesting potential sites and mechanisms of action. Pharmacokinetic studies of glucosamine and chondroitin to date have been limited by uncertain product quality, study design, sample size, and problematic assay methods. The present availability of a plasma assay that is sensitive and specific combined with a properly designed and controlled pharmacokinetic trial on a sufficient number of human subjects will provide the necessary information to fully characterize both the single-dose and steady-state pharmacokinetics of each of these agents.